171117 Depression PC V2 db ns · Primary Care Treatment Strategies for Depression: Childhood Through Young Adulthood December 6th, 2017 David A. Brent, MD University of Pittsburgh

Primary Care Treatment Strategies for Depression: Childhood Through Young Adulthood

December 6th, 2017

David A. Brent, MDUniversity of Pittsburgh School of Medicine 1

David Brent, MD

University of Pittsburgh Medical Center/School of Medicine

December 6, 2017

DisclosuresFunding from NIMH

Scientific Board, Klingenstein Third Generation Foundation

Scientific Board, AFSP

Member, NIMH Council

Royalties from Guilford, UpToDate, eRT

Consultant, Healthwise


December 6th, 2017


Objectives

Describe the latest guidelines for treating major depressive disorder (MDD) in children, adolescents and young adults;

Identify barriers to appropriate treatment of those with MDD; and,

Discuss how HCPs can implement best practices for treating MDD in the clinical setting.

What does depression look like? Clinical diagnosis with depressed mood and/or boredom/anhedonia– most days for >2 weeks + 4 more symptoms:

Worthlessness

Impaired concentration

Suicidal ideation/behavior

Guilt

Impaired sleep

Impaired appetite

Functional impairment


December 6th, 2017


Why is it important to screen?Very common– about 20% have at least one episode during adolescence

Less than 50% of depressed youth are getting diagnostic‐specific treatment

The longer the depression, the harder it is to treat

Sequelae of untreated depression Associated with long term relational, educational, and occupational attainment

Bi‐directional relationship with alcohol and substance abuse

Associated with other risk behaviors

Dramatically increases the risk of suicide attempts and suicide

Health care costs of untreated depression are $2726 higher than in non‐depressed youth


December 6th, 2017


Differential DiagnosisBipolar spectrum– presence of hypomania, mania, suspect with family history, psychotic depression

Seasonal affective disorder—most commonly fall/winter, hypersomnia, low energy, carbohydrate craving, respond to light treatment

Psychotic depression—associated with depression temporally, often, but not always in content

Differential Diagnosis

Disorder Differential

ADHD Demoralization due to peer, school, family problems, improves with treatment

Asperger’s Demoralization due to peer rejection

Anxiety Disorder

Dysphoria only in anxiogenic situations

OCD Upset by obsessive thoughts, impairment due to rituals, OR inability to complete them

EatingDisorder

Secondary to nutritional issues, reverses with weight restoration; may also be sad because being forced to gain weight


December 6th, 2017


Differential Diagnosis

Disorder Differential

ConductDisorder

Precipitated by legal/disciplinary difficulties, but also peer and family conflict, erosion in developmental competencies

Substanceuse

Can mimic affective symptoms, temporal order, change with abstinence

Pre‐psychosis

Abnormal development prior to onset, family history, course

Medicalillness

Fatigue, concentration, anhedonia secondary to illness or treatment

Medical conditions that can mimic or contribute to depression Anemia

Thyroid disease

Occult inflammatory disorders

Mononucleosis

Lyme disease

Sleep apnea

Low folate

Low Vitamin D

Diseases of inflammation

IBD

Asthma

Eczema

CNS diseases

Epilepsy

Migraine

MS

Concussion


December 6th, 2017


Get lab tests on everyone?

Very low yield, so not on everyone

Very prominent fatigue in the absence of prominent sleep disorder

Depression unresponsive to first treatment (some would wait longer)

Detecting and Assessing Depression

Well‐child care PHQ‐9

On the basis of other risk factors

Parental depression

History of maltreatment

Bereavement

Concussion

Peer victimization

ADHD, Anxiety, ODD

On the basis of other behaviors

Change in level of function and motivation

Withdrawal from friends

Risk‐taking behavior

Frequent service use

Somatic complaints

Self‐harm

Sleep or appetite changes.


December 6th, 2017


Patient Health Questionnaire (PHQ)*

Version Sensitivity Specificity

PHQ‐2>3 74% 75%

PHQ‐9>11 89.5% 77.5%

*Richardson et al., 2010a,b

Prediction of persistent depression at 6 months, 16% increased likelihood for each point increase in PHQ‐9 above 11

Over the past 2 weeks, how often have you been bothered by any of the following problems

Not at All

Several Days

MoreThan Half the Days

Nearly Every Day

1. Little interest or pleasure in doing thing

0 1 2 3

2. Feeling down, depressed or hopeless

0 1 2 3

Patient Health Questionnaire (PHQ‐2)


December 6th, 2017


3. Trouble falling asleep, staying asleep, or sleeping to much

0 1 2 3

4. Feeling tired or having little energy 0 1 2 3

5. Poor appetite or overeating 0 1 2 3

6. Feeling bad about yourself – or that you’re a failure or have let yourself or your family down

0 1 2 3

7. Trouble concentrating of things, such as reading the newspaper or watching television

0 1 2 3

8. Moving or speaking so slowly that other people could have noticed. Or, the opposite – being so fidgety or restless that you have been moving around a lot more than usual

0 1 2 3

9. Thoughts that you would be better off dead or of hurting yourself in some way

0 1 2 3

Now that you’ve screened, then what? PHQ‐2 or 2 or greater– do rest of PHQ‐9

PHQ‐9 of 10 or greater

Slightly lower scores– ask how they are doing, watch them and re‐screen in 1 month.

Sleep item correlates highly with Insomnia Severity index

Suicide item predicts future attempts and suicides (Simon et al., 2013)


December 6th, 2017


Talking points According to your screen, it is likely that you are depressed. I cannot promise complete confidentiality–things that could have a severe effect your health I need to disclose, but I will not tell your parents anything without discussing it with you first.

I would like to follow‐up with a few questions:

Are you having difficulty with school, friends, parents?

Assess suicidal thoughts and plans (more about that later)

A more thorough assessment would be a good idea

After that, we can come up with some ideas for treatment? Does that sound okay?

Need to also get parents on board

If a patient discloses that he/she is suicidal To what extent to you intend to carry this out?

Do you have a plan?

Do you have a location picked out?

What is keeping you from acting on your suicidal thoughts

What would drive you to act on your thoughts in the future?

Don’t promise absolute confidentiality.


December 6th, 2017


Developing a safety plan in a hurryWhat are triggers for your suicidal thoughts (or what makes them worse)?

What are your reasons for staying alive?

What can you do to avoid these triggers?

How can we cope with these triggers?

Distraction

Review of Reasons for Living

Relaxation/Deep breathing/Mindfulness

Reaching out to other people

Reaching out to professionals

Emergency help

Launching the Safety PlanAsk patient to explain plan to parents

Get parental feedback

Ask both parents and patient what might get in the way of implementing the plan

Consider either ways to overcome those barriers, or revision in the plan

Removal/securing lethal agents


December 6th, 2017


When to Refer for Emergency Evaluation Clear expression of suicidal intent and unwilling to commit to safety plan.

Clinical conditions that would impede ability to adhere to a safety plan:

Psychosis

Bipolar disorder– rapid cycling or mixed state

Alcohol and drug abuse

Traumatic brain injury

The lower parental support and monitoring, the lower your threshold for emergency referral should be.

Addressing common barriers to treatment

Barrier Possible response

Hopeless and low motivation These are symptoms of depression. What might motivate you to give it a try for a few sessions to see if it could make some difference?

Alternative explanation (“justwants attention”, “just normal adolescence”)

Depression is “no one’s fault.” It is disease like diabetes, with biological changes in the brain that affect mood and motivation.

Mental health treatments are ineffective or take forever to work

There are several good alternativetreatments that are effective in a matter of 2‐3 months


December 6th, 2017


Barriers Possible Response

Afraid of institutionalization, medication, ECT, etc.

• You and your parents get to choose what kind of treatment you want.

• No one will force you to take medication and there are good alternatives.

• At present, your depression does not require hospitalization, which we would only do if we were concerned about your safety.

Cost, time from work, travel, school • We can try to identify a sliding fee or a lower cost provider.

• The treating clinician can conference you on the phone to update you for at least some meetings.

• We can try to find someone closer to your home.

• We can help get school accommodations, and find times after school.

Getting the patient and parent to pursue treatment Education about depression– it is a brain disease that often runs in families and is no one’s fault.

It is highly treatable. 80% of people recovery fully with proper treatment within one year.

Treatment and recovery takes time and time investment.

It is often recurrent so we will need to make a life plan for prevention.


December 6th, 2017


Depression is a disease

Runs in families, about 50% effects are genetic

Has alterations in neurotransmitters in the brain

Altered connectivity and processing of emotional material

High reactivity and bias toward negative emotional cues

Low pre‐frontal modulation of emotional responses

Low reward response

High amount of self‐reference (associated with rumination)

Natural History of Depressive Disorders Persistent depressive disorder– high risk of MDD, bipolar disorder, average duration > 5 years

MDD– average episode length 4‐8 months

Recurrence– 40% in 5 years, nearly 100% by adulthood, especially in adolescent‐onset

Risk of bipolar disorder around 10‐20%

psychotic depression

family history of bipolar disorder

previous hypomania, even during treatment


December 6th, 2017


Most people can be helped Psychotherapy

Cognitive behavior therapy

Interpersonal therapy

Attachment‐based family therapy

Medication– one best studied and most effective is fluoxetine

Response rates for both around 60% by 12 weeks, 80% by 24 weeks

If don’t respond to the first medication, 50% response to second intervention

When can the patient be treated as an outpatient? Adequate level of function– self‐care, school attendance

No imminent harm to self or others

Diagnostic impression is clear

Patient and family likely to be adherent

Other levels of care besides hospital Partial hospital

Intensive outpatient programs

Home‐based family‐centered care

Case management


December 6th, 2017


Deciding which patients to manage Patient can be treated on an outpatient basis Is not at imminent risk for suicide Does not have a co‐morbid condition that would interfere with the treatment of depression Alcohol and substance abuse Eating disorder Comorbid medical illness that is interacting with depression (e.g., diabetes, asthma)

Severe sleep problems

Bipolar, psychotic Contextual factors that require psychotherapy

Family discord or maltreatment Peer victimization Issues of sexual orientation or gender identity

Guidelines for treatment of adolescent depressionMild depression: watchful waiting and support

Moderate depression: either medication or psychotherapy (CBT, IPT, ABFT)

Severe and/or treatment resistant depression (combination treatment)

Duration of initial treatment 8‐12 weeks

Then need continuation treatment for at least 6 months after symptom response


December 6th, 2017


Making a treatment plan

Treatment preferences and availability

Level of impairment

Comorbidity

Contextual factors

Important contributors that factor into treatment plan Parental depression

Parent‐child discord

Maltreatment– especially if ongoing or threatened

Assault

Peer victimization

Academic difficulties

Bereavement


December 6th, 2017


Indicated psychotherapies for adolescent depression Cognitive Behavior Therapy (CBT)

Cognitive restructuring

Social skills and problem solving

Behavior activation

Interpersonal Therapy (IPT)

Alter interpersonal relationships to make them more rewarding, less discordant

Family‐based Attachment Therapy

Improves connection between parent and child

Antidepressants in MDD Fluoxetine (FLX) (NNT=5), Escitalopram FDA‐approved.

Citalopram=FLX<Paroxetine in TORDIA

Paroxetine– overall not shown effective

Sertraline (NNT=10)

Venlafaxine—post‐hoc show efficacy in adolescents, not kids (low doses used). In TORDIA, VLX=SSRI.

Nefazodone– One positive trial, rarely used due to hepatotoxicity (1/1,000,000 doses)


December 6th, 2017


Antidepressants in MDD (Cont.)

Bupropion– Open trials positive, never been studied with RCT and probably never will be

Atomoxepine– Not effective

Mirtazapine, one trial, negative

Tricyclic antidepressants– Not effective, don’t use! May be helpful as augmenting agent, in management of migraine

Effects of Antidepressant by Age (Risk Difference) (Bridge et al., 2007)

Indication Children Adolescents

MDD 7% 13%

MDD‐FL 20.5% 20.0%

OCD 24% 18%

ANX 29% 46%


December 6th, 2017


SSRIs and suicidal events Increased risk of suicidal events (new or increased ideation or attempt) in drug vs. placebo in RCTs– risk difference: 0.9%

Response rate 10% risk difference: so 11 times more patients will respond than will have a suicidal event.

Pharmacoepidemiological studies show that increased prescription of SSRIs associated with a decrease in suicide rate and vice versa

Due to Black Box Warning, decline in SSRIs, diagnosis of depression, units of treatment in adolescents

Dose, Concentration, and ResponseNon‐responders more likely to respond to an increased dose of fluoxetine vs. continuing at the same dose (Heiligstein, 2007)

Dose and plasma concentration are both related to serotonin transporter binding in vitro

Around 80% binding is associated with response

Response associated with higher levels and greater adherence (Sakolsky, 2011; Woldu, 2011)


December 6th, 2017


SSRIs: Half‐LivesDrug Half‐life Developmental Effect

Fluoxetine 4-6 daysHigher levels in children than adults

Paroxetine 11 hoursHigher levels in children than adults

Sertraline 15.3-20.4 hrs.Non-linear, lower than in adults

Citalopram 16.4-19.2 hrs. Lower than in adults

Venlafaxine 9-13 hrs. Lower than in adults

Nefazadone 3.9 vs. 7 hrs. Lower than in adults

Implications of Pharmacokinetics of Antidepressants

Need adequate exposure to affect serotonergic reuptake inhibition; 5 times the half‐life to achieve steady state

For many drugs, half‐life is shorter than in adults

Therefore, may need higher doses/BID doses in order to achieve response and avoid withdrawal effects.

Sertraline has non‐linear kinetics; this is most relevant at lower doses.


December 6th, 2017


Some general guidelines for antidepressant use with adolescents Both parent and adolescent must be on board and understand risks and benefits

Start low, go slow

Need to see weekly for first 4 wks, then every other week until week 12

Don’t change dosage more frequently than every 3‐4 weeks

Monitor for symptom change, suicidal ideation/behavior, and side effects

Ultimate goal is remission

Topics to cover in session

Overall functionMood (1‐10, can fill out PHQ‐9)Suicidal thoughts (how often, intensity, can resist?, plan, what will push in either direction?)

SleepOther side effectsAdherenceSafety plan

42


December 6th, 2017


Recommended visit schedule

Weekly for first 4 weeks

Every other week until week 12

Monthly for next 6 months.

Can do some of this over the phone

Dosing Parameters

Drug Dose (Week)

1 2 3 4 5 6 7 8 Range

Fluoxetine 10 20 20 20 40 20-80 mg

Citalopram 10 20 20 20 40 10-40 mg

Escitalopram 5 10 10 10 20 10-40

Sertraline 25-50 50-100 100-150 50-200

Venlafaxine XR 37.5 75 150 150-375

Bupropion XL 100-150 300 150-450


December 6th, 2017


FDA warning about citalopram

Citalopram may cause QTc prolongation

Therefore, do not go above 40 mg

Get baseline ECG, prior to, and after each dose increase

Related to metabolite didemethylcitalopram (DDCT) (in beagles!)

Contraindications to antidepressants

Mild to moderate depression– just as likely to respond to psychotherapy

Psychosis– needs an antipsychotic in addition

Mania or family history (then use very carefully)

Allergy


December 6th, 2017


Side Effects of SSRIs

• Nausea, weight loss, weight gain

• Nervousness, restlessness (fluoxetine)

• Sleep difficulties, vivid dreams (monitor and manage)

• Disinhibition, memory problems, irritability

• Mania • Sweating

• Lower clotting time/easier bruising

• Fatigue (sertraline, fluvoxamine, paroxetine)

• Sexual side effects

Management of side effects

Akathisia, irritability, increased depression, mania, significant cognitive changes– need to stop drug.

Risk of mania about 10% vs. .45% drug vs. placebo

If have responded but still irritable, will add DBT or CBT, lithium, antipsychotic, or lamotrigine

Weight loss, usually transient, can add mirtazapine

Weight gain, can switch to another SSRI


December 6th, 2017


Sleep Difficulties / FatigueR/O medical causes, sleep apnea, restless legs syndrome

Shift or divide dose

Sleep hygiene

CBT for insomnia

Diphenhydramine, melatonin, mirtazapine

For fatigue and residual symptoms, augmentation with bupropion

Withdrawal Syndrome

Result of abruptly stopping SSRI or SNRI

Flu‐like symptoms– Malaise, GI distress, dizziness, anxiety, dysphoria

Taper gradually, warn patient about possibility


December 6th, 2017


Drug Interactions & SSRIs

NSAID and GI bleeding

Tryptans, Linezolid– serotonin syndrome

2D6 (FLX)– increase levels of haloperidol, risperidone, opiates, TCAs

3A4 (NFL)– sertraline, TCAs, benzodiazepines, carbamazepine

Bottom line: No one can remember all of these drug interactions; check with the hospital pharmacy!

How to recognize Serotonin Syndrome

Most common in those with polypharmacy

Spontaneous clonus

Inducible clonus or ocular clonus + agitation or diaphoresis

Tremor + hyper‐reflexia

Hypertonia + >38 C temp + ocular clonus or spontaneous clonus


December 6th, 2017


Treatment of Serotonin Syndrome

D/c Serotonergic agents

Benzodiazepines for agitation

Supportive treatment

Cyproheptadine– serotonergic antagonist

Approach to Patients with Suboptional Response

Document improvement and lack thereof

Establish adherence and adequacy of treatment, evaluate exposure

Psychosocial stressors

Comorbid illness, sleep

Medication side effects

Convey hope


December 6th, 2017


Residual Symptoms: Management Augment vs. switch– if had response, but still significant residua and no side effects

Anhedonia: activity scheduling, bupropion

Sleep difficulties: sleep hygiene, melatonin, mirtazapine, sleep studies

Irritability: psychotherapy, lithium, antipsychotic (for the latter two, must be severe)

Fatigue: sleep hygiene, switch time of dosage, add buproprion (and rule out other medical causes). Behavior activation

Treatment Resistant Depression Switch to second SSRI (as good as switching to venlafaxine and fewer side effects)

Consider bupropion if prominent fatigue, ADHD, does not have prominent anxiety

Consider SNRI if has prominent pain syndrome like migraine, fibromyalgia, also good for comorbid anxiety

After that: nefazodone (comorbid anxiety), lamotrigine, MAOI, augmentation with lithium, T3, or antipsychotic augmentation


December 6th, 2017


Continuation treatmentHigh risk of relapse unless continue treatment for 6‐12 months after complete symptom relief– timing also based on practical considerations.

For people with recurrent or chronic depression, may want them to continue in treatment longer

Same dose of medication as got them well

Addition of CBT helpful

Special issues with patients going to college Depression is a life‐long issue

Choose a school with reasonable supports, accomodations, and resources for MH treatment

Make sure have an appointment set up

Prepare for transition Have fill own prescriptions and make own appts.

Anticipate challenges Sleep

Roommates

Alcohol/Drugs

Academic challenges


December 6th, 2017


Implementation in your practice Have a response plan for positive screens, including suicidal ideation

Decide what level of complexity and severity you are comfortable treating

Have trusted referral sources handy

Provide education and motivation, taking into account patient and parent treatment preferences

If manage antidepressants in your practice, follow frequently and assess suicidality, side effects, and response, prepared to switch if non‐response

Collaborative care Co‐located– makes referral and collaboration much easier

Nurse clinicians‐ can do medication and psychotherapy

Psychotherapists

Communication with PCP so that can handle any office or after hours calls

Telepsychiatry– for areas where on‐site available of mental health specialists is limited


December 6th, 2017


Summary points Adolescent depression is a life‐long, often recurrent illness that requires long‐term management

Screening with the PHQ‐9 is an quick and effective way to detect most depressions

Bipolar disorder is the most important differential

Psychoeducation about depression, conveyance of hope, hearing treatment preferences and barriers to treatment are a key part of making an effective referral

Evidence‐based psychotherapies and medications are effective in helping the majority of depressed youth to recover

Continuation treatment to prevent relapses

Transition plan when patient leaves home to take more responsibility for own care.

Thank you for your attention!

171117 Depression PC V2 db ns · Primary Care Treatment Strategies for Depression: Childhood Through Young Adulthood December 6th, 2017 David A. Brent, MD University of Pittsburgh

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